Systems and methods for delivery of gel embolics

ABSTRACT

Delivery systems for liquid embolics and methods of using them are disclosed. The devices generally include a catheter and one or more retention elements to limit migration of the liquid embolic to non-target sites.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority under 35 USC § 119 toU.S. patent application Ser. No. 15/089,084 filed Apr. 1, 2016, whichclaims priority to U.S. Provisional Patent Application Ser. No.62/141,536, filed Apr. 1, 2015, both of which are incorporated byreference herein in their entirety and for all purposes.

FIELD OF THE INVENTION

This application relates to the field of medical devices. Moreparticularly, the application is related to devices and methods for theocclusion of blood vessels and/or the delivery of drugs to patients.

BACKGROUND

Embolization involves the partial or complete occlusion of bloodvessels, limiting the flow of blood therethrough. The intentionalocclusion of blood vessels (“therapeutic embolization”) may be used totreat a variety of vascular and non-vascular conditions includingcerebral and peripheral aneurysms, arteriovenous malformation, anduterine fibroids and to reduce blood flow to solid tumors includingliver tumors. Embolization may be achieved by any number of means,including through the use of polymer microspheres, metal coils or plugsand liquid embolic materials.

In a typical embolization procedure, local anesthesia is first givenover a common artery or vein. The artery or vein is then punctured and acatheter is inserted and fluoroscopically guided into the area ofinterest. An angiogram is performed by injecting contrast agent throughthe catheter, thereby visualizing the portion of the vascular treedownstream of the distal end of the catheter. Once the catheter ispositioned in a site where deposition of an embolic agent is desired,the composition or agent is deposited through the catheter. The embolicagent is generally selected based on the size of the vessel to beoccluded, the desired duration of occlusion, and/or the type of diseaseor condition to be treated, among others factors. Following delivery ofthe embolic agent to the site within the vessel to be occluded, afollow-up angiogram can be performed to determine the specificity andcompleteness of the occlusion.

In many common embolic procedures, including sandwich embolization ofsplanchnic aneurysms, sandwich embolization of gastrointestinal bleeds,embolization of vessels to treat varioceles or pelvic congestionsyndrome, and embolization to arrest hemorrhage after trauma,embolization is desired along of a length of blood vessel, rather thanat a focal point. However, embolic coils, which are most commonly usedin embolization procedures, are optimally used in focal embolizationapplications. In practice, users may use multiple embolic coils to packand fill the length of the vessel, but this approach is time- andmaterial-intensive, as many coils must each be placed individually,increasing the costs of such procedures.

Liquid and swellable embolics have recently emerged as a potentialalternative to coil-packing procedures. Throughout this disclosure, theterms “liquid embolics,” “gel embolics” and “swellable embolics” areused interchangeably to refer to (a) flowable polymerizing embolicmaterials, which include TRUFILL® n-Butyl Cyanoacrylate (n-BCA) (Codman& Shurtleff, Inc., Raynham, Mass.) and ONYX® ethylene vinyl alcoholcopolymer (EVOH) (ev3 Endovascular, Inc., Plymouth, Minn.), as well as(b) absorbent or superabsorbent polymer embolics, such as collagenocclusive plugs These materials can be expensive (up to $2,500 per mL inthe case of EVOH embolics) and, when deployed in vessels with relativelyhigh flow rates, may be prone to migration and embolization ofnon-target areas. To prevent such migration, practitioners may deploycoils on the proximal and/or distal ends of a region being embolized, inorder to reduce blood flow thereto. This approach, however, alsorequires multiple steps, and may require the use of multiple catheters,particularly when using liquid embolics (such as n-BCA) solidify withinthe catheter, necessitating the placement of a new catheter ifdeployment of an embolic coil proximal to the already polymerizedembolic mass is desired.

Another alternative to packing vessels with conventional embolic coilsand/or liquid embolics is to use multiple hydrogel-coated embolic coils,such as the AZUR™ coil (Terumo Medical Corporation, Somerset, N.J.);these coils expand radially when exposed to aqueous environments,allowing them to occupy more space than conventional embolic coilshaving an equivalent pre-deployment diameter. Even so, proceduresinvolving these devices will typically require placement of multiplecoils, and will thus involve greater complexity and expense thaninterventions which require only a single deployment step.

SUMMARY OF THE INVENTION

The present invention, in its various aspects, addresses theshortcomings of existing coil and liquid embolics, and provides systemsand methods for single-step delivery of embolics across a vascularlength, rather than at a focal point.

In one aspect, the present invention relates to a system for treating apatient that includes a catheter, one or more retention elementsslidably disposed within the catheter, and an embolic material that isflowable through, or slidably disposed in, a lumen of the catheter. Thesystem also optionally includes an elongate body connected to theretention element(s), such as a shape memory wire, which wire in turncan include a detachable link such as an electrolytically severalsegment, a mechanical link, and a thermally severable segment. Theretention element, which is generally (but not necessarily) moveablebetween a compressed configuration with a first diameter and an expandedconfiguration with a second, larger diameter, may have a spiral shape ora plurality of cross members (among other structures) and may besubstantially planar when unconstrained, or it may form a more3-dimensional structure. In some embodiments, the system includes tworetention elements, one positioned proximally to the embolic material,the other distally, and optionally includes (i) a pushrod slidablydisposed within the catheter and proximally to the most proximalretention element, and/or (ii) a retention element extending between theretentive elements and connecting them. In some instances, the embolicmaterial absorbs water and/or forms a gel. These systems are useful inmedicine, particularly in embolization of body lumens, and moreparticularly in vascular embolization procedures. An exemplary procedureutilizing such a device includes inserting the distal end of thecatheter into a blood vessel, advancing the retention element distallyfrom the catheter into the blood vessel, and disposing the embolicmaterial proximally to the retention element through the catheter.

In another aspect, the present invention relates to a system fortreating a patient that includes a catheter, an embolic material that isslidably disposed within the lumen of the catheter with first and secondretention elements disposed proximally and distally about the embolicmaterial, respectively, and a pushrod that slides within the catheterand is positioned proximally to the first retention element. The embolicmaterial preferably (but not necessarily) absorbs water and/or forms agel, and it may include collagen or another polymer, for example as asuperabsorbent polymer plug.

In yet another aspect, the present invention relates to a method fortreating a patient that includes a step of forming an occlusivestructure within a blood vessel of a patient. The structure generallyincludes an expandable implant and a polymer plug contacting theimplant, which plug includes or is formed by a liquid embolic materialand/or a superabsorbent polymer material. The implant can include one ormore retentive elements having structures—and in structuralrelationships to the plug—as described above.

DRAWINGS

Aspects of the invention are described below with reference to thefollowing drawings in which like numerals reference like elements, andwherein:

FIG. 1A through 1E shows schematic views of delivery systems accordingto certain embodiments of the invention in various stages of deployment.

FIG. 2A through 2C shows schematic views of retention elements accordingto certain embodiments of the invention, while FIG. 2D shows a schematicview of a delivery system according to the invention in use in aprocedure to occlude a blood vessel having a disrupted wall.

FIG. 3A through 3C shows schematic views of delivery systems accordingto certain embodiments of the invention in various stages of deployment.

Unless otherwise provided in the following specification, the drawingsare not necessarily to scale, with emphasis being placed on illustrationof the principles of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Turning to FIG. 1, an exemplary delivery system 100 according to onegroup of embodiments of the present invention comprises a catheter 105and, slidably disposed within the catheter 105, a shape memory wire 110that includes a retention structure 115 at its distal end. The retentionstructure 115 is, generally, radially compressible and expandable, topermit its insertion through a relatively narrow-gauge catheter bore toat least partially occlude a larger-diameter blood vessel. In general,the systems and methods of the present invention will be used inarteries ranging from 2-8 mm in diameter and veins ranging from 1-10 mmin diameter. The retention structure 115 can have any suitable shape toachieve such radial compression/expansion and, when expanded, to impedeor prevent the flow of viscous materials such as liquid embolics and/orto prevent or limit migration of superabsorbent polymer embolic plugs.These shapes include, without limitation, a spiral shape (as shown inFIG. 2A) or a cruciate shape (shown in FIGS. 2B-C) comprising anysuitable number of cross-members, including two, four, six, eight,etc.). The retention structure 115 also optionally includes a covering,such as an electrospun fiber matrix, comprising a polymer such aspolytetrafluoroethylene (PTFE), expanded PTFE, polyethyleneterephthalate (PET), polyvinylidene fluoride (PVDF), and the like.

Wire components of the delivery system 100, including the shape memorywire 110 and the retention element 115, are preferably made of a shapememory alloy such as nitinol, though other materials can be used such asstainless steel, shape-memory polymers, platinum, or poly-lactic acid(PLA) and/or poly-lactic-co-glycolic acid (PLGA). If a coating is used,it may be hydrophilic (e.g. Bioslide™ hydrophilic coating, BostonScientific, Marlborough, Mass.), or hydrophobic (e.g.polytetrafluoroethylene (PTFE), silicone). The shape memory wire 110and/or retention element 115 can also include an iodinated coatingand/or a discrete fluoroscopic marker such as a platinum, palladium ortungsten band or other marker. If a severable link or joint is used, itcan take any suitable form, including electrolytically severable links,thermally severable links, frangible links, and mechanical joints suchas knotted tethers, male and female screw-ends, ball and socketmechanisms, etc. Exemplary detachment mechanisms for medical implantsare described in, inter alia, U.S. Pat. No. 5,250,071 (describinginterlocking clasp mechanisms incorporating complementary male andfemale ends), U.S. Pat. No. 5,354,295 (describing electrolyticallyseverable core wires), U.S. Pat. No. 6,059,779 (describing annularreturn electrodes disposable about electrolytically severable corewires), and US pre-grant publication no. 20090177261 (describingdetachment mechanisms utilizing materials that change shape in responseto the application of heat or electrical energy, including syntheticpolymers). Each of the foregoing references is hereby incorporated byreference in its entirety and for all purposes.

Retention elements 115 are shown in the drawings as being substantiallyplanar, but other 3-dimensional shapes are used in various embodiments,including without limitation multiple spirals in multiple planes,birds-nest shapes, etc. The retention element 115 may also comprise amesh and/or a textured surface to facilitate adhesion to the vesselwall. And, although the retention element 115 is described above asgenerally self-expanding, it can be, alternatively or additionally,expandable by means of a separate device or element, or by theapplication of an external stimulus such as the application of currentor heat (e.g. expanding in response to a temperature change wheninserted into the body) or may be physically expanded by asuperabsorbent polymer plug as it expands in situ. In addition, in someembodiments, the retention element 115 is a detachable balloon.

In use, the delivery system 100 is used to deliver a liquid embolic orsuperabsorbent plug 120 into a blood vessel, according to a processgenerally illustrated in FIGS. 1A-E. The process begins with theinsertion of the catheter 105 into the patient's vasculature, such thata distal end of the catheter 105 is proximate to, or within, a length ofblood vessel where occlusion is desired. When the catheter 105 ispositioned, the shape memory wire 110 is extended distally through adistal aperture of the catheter 105 and into the vessel. As it isextended, the retention element 115 at the distal end of the shapememory wire 110 preferably expands radially outward to contact aninterior wall of the blood vessel. In preferred embodiments, thecatheter 105 is positioned so that the retention element 115 is at ornear its intended deployment site, then the catheter 105 is retracted,unsheathing the retention element 115 and the embolic material 110.Thereafter, a liquid embolic 120 is flowed through the catheter into thespace defined by the distal end of the catheter 105 and the retentionelement 115. The liquid embolic 120 can be any material thatpolymerizes, cross-links, viscifies, or otherwise changes from a liquidto a gel or solid in situ (which processes are referred to throughoutthis application, for ease of presentation, as “hardening”) followingdeployment into a blood vessel, such as n-BCA or EVOH.

After the liquid embolic 120 has hardened, the shape memory wire 110 isoptionally severed, such that the retention element 115 and a distalportion of the wire 110 remain in place and attached to the embolicmaterial 120 so as to form, together with the embolic material 120, anindwelling implant. Severing of the shape memory wire 110 isfacilitated, in preferred embodiments, by the use of a severable link orjoint 111, which can be a mechanically, electrolytically or thermallyseverable structure formed in the shape memory wire. In some alternativeembodiments, however, the wire 110 is simply retracted back into thecatheter 105 through the hardened embolic material 120; in theseinstances, retraction may be facilitated by a lubricious, hydrophobic orother coating on the wire 110, which coating prevents the wire fromsticking to and disrupting the hardened embolic 120. Retraction of theshape memory wire 110 through the plug is also optionally facilitated bythe use of a multi-lumen catheter 105, and the positioning of the shapememory wire 110 in a first lumen while the liquid embolic 120 is flowedthrough a second lumen. The second lumen can, also optionally, be largerin diameter than the first lumen, and the first lumen can alsooptionally be laterally offset from a central axis of the catheter 105,thereby placing the shape memory wire 110 adjacent to the wall of theblood vessel when deployed.

Delivery systems according to these embodiments may be particularlyuseful in embolization procedures for stopping hemorrhage, as shown inFIG. 2D. An exemplary deployment procedure for these applications issimilar to the exemplary procedure described above with these additionalconsiderations: the distal end of the catheter 105 is positionedproximate to (e.g. just proximal of) a disruption 1 in the wall of theblood vessel to be embolized, then the shape memory wire 110 is extendedacross a length of the blood vessel that spans the disruption 1, so thatthe retention element 115 is positioned distal to the disruption 1. Withthe delivery system so positioned, the liquid embolic 120 is flowed intothe vessel so as to occlude the length of the vessel comprising thedisruption 1, and the procedure continues as described above.Alternatively, the delivery system can be positioned proximally to (i.e.upstream of) the disruption 1, so that the deployment of the liquidembolic 1 interrupts blood flow to the disruption 1. Delivery system 100is also useful more generally in procedures in which the targetvasculature is not “end-organ,” and downstream, non-target embolizationis possible.

A second group of preferred embodiments, shown in FIG. 3 A-C, alsoutilize a catheter 205, but omit the shape memory wire in favor of firstand second retentive elements 210, 211 which are placed about theproximal and distal ends of a bolus of embolic material 215. Each of theretentive elements 210, 211 and the embolic material 215 are slidablydisposed within the catheter 205, which optionally includes a pushrod206 to apply force to the proximal retention element 210 and the embolicmaterial 215. When a pushrod 206 is used, it is optionally reversiblyattached to the proximal retention element 210 by means of interlockingarms, a screw, or any other suitable means.

In a typical embolization procedure using a delivery system according tothis group of embodiments, the catheter 205 is positioned so that itsdistal end is adjacent to, or within, a length of blood vessel in whichembolization is desired. For instance, in the sequence shown in FIG.3A-C, the distal end of the catheter 205 is advanced so that the distaltip of the catheter 205 lies at a distal-most extent of the length ofblood vessel where embolic material 215 will be provided. To deploy theretention elements 210, 211 and the embolic material 215, the catheter205 is retracted over the pushrod 206, preventing retraction of theretention elements 210, 211 and the embolic material 215. Both theretention elements 210, 211 and the embolic material 215 are preferablycapable of radial expansion, allowing the occlusion of blood vesselshaving inner diameters larger than the bore of the catheter 205. Afterthe catheter 205 is retracted and the retention elements 210, 211 andthe embolic material is positioned, the pushrod 206 can be retracted andthe catheter 205 removed. As above, the delivery system 200 isparticularly useful in embolization procedures for the treatment ofhemorrhage, in which the distal end of the catheter is positioned sothat the embolic material will span a length of the blood vessel thatincludes a disruption in its wall.

In addition to deployment by retraction of the catheter, the retentiveelements 210, 211 and the embolic material 215 can be pushed out of thedistal end of the catheter 205 by advancing the pushrod 206 distally.

The catheter 205 is provided in multiple sizes, including withoutlimitation 5 French (1.667 mm or 0.066″) which is suitable for treatinglarger structures such as varioceles, 0.027″ (0.69 mm) inner diameter,and 0.021″ (0.53 mm) inner diameter, which may be used to embolize sitesof bleeding in the gastrointestinal tract, splenic aneurysms, and thelike.

The distal retention element 211 can have a shape similar to the shapesdescribed for retention element 115 above and shown in FIG. 2, but canalso be tapered or football shaped. Together with the proximal retentionelement 210, the distal retention element 211 spatially constrains theembolic material, limiting its migration within the blood vessel.

The embolic material 215 is preferably made of a superabsorbent polymerwhich absorbs water from the bloodstream to expand to fill the vessellumen, including without limitation compressed collagen. The embolicmaterial 215 can also include a rigid spacing element (not shown) madeof, e.g., nitinol to ensure that the plug retains a fixed length. Thespacing element can be attached, in some cases, to one or both of theretention elements 210, 211. Devices of the invention can come in anynumber of sizes (lengths, diameters) for use in a variety ofapplications including trauma, varicocele, pelvic congestion syndrome,peripheral aneurysm, gastrointestinal bleeding, etc. Devices of theinvention can also be used in both arterial and venous systems.

The delivery systems of the invention, and their various components, aremade using materials and techniques that are well established in thefield. For instance, shape memory wires 110 and retentive elements 115,210, 211 can be made by coiling or laser-cutting to shape andheat-setting. Catheter bodies can be made by extrusion or by means ofcoated mandrels, or any other suitable method.

Delivery systems according to these embodiments possess severaladvantages relative to the current state of the art. First, thesedevices allow rapid, one-step deployment of liquid embolics and,simultaneously, of retentive structures that reduce or even preventmigration of the liquid embolics beyond the site of deployment. Thesedevices require only a single catheter and single intervention,promoting shorter procedure times, and are made using low cost, commonmaterials that are known to those of skill in the medical implant andcatheter fields. Additionally, the volume of the liquid embolic appliedcan be controlled finely by the user at the time of deployment, allowingsystems and methods of the present invention to embolize a range ofvessel volumes and sizes without the need for significant customizationor alteration.

The phrase “and/or,” as used herein should be understood to mean “eitheror both” of the elements so conjoined, i.e., elements that areconjunctively present in some cases and disjunctively present in othercases. Other elements may optionally be present other than the elementsspecifically identified by the “and/or” clause, whether related orunrelated to those elements specifically identified unless clearlyindicated to the contrary. Thus, as a non-limiting example, a referenceto “A and/or B,” when used in conjunction with open-ended language suchas “comprising” can refer, in one embodiment, to A without B (optionallyincluding elements other than B); in another embodiment, to B without A(optionally including elements other than A); in yet another embodiment,to both A and B (optionally including other elements); etc.

The term “consists essentially of” means excluding other materials thatcontribute to function, unless otherwise defined herein. Nonetheless,such other materials may be present, collectively or individually, intrace amounts.

As used in this specification, the term “substantially” or“approximately” means plus or minus 10% (e.g., by weight or by volume),and in some embodiments, plus or minus 5%. Reference throughout thisspecification to “one example,” “an example,” “one embodiment,” or “anembodiment” means that a particular feature, structure, orcharacteristic described in connection with the example is included inat least one example of the present technology. Thus, the occurrences ofthe phrases “in one example,” “in an example,” “one embodiment,” or “anembodiment” in various places throughout this specification are notnecessarily all referring to the same example. Furthermore, theparticular features, structures, routines, steps, or characteristics maybe combined in any suitable manner in one or more examples of thetechnology. The headings provided herein are for convenience only andare not intended to limit or interpret the scope or meaning of theclaimed technology.

Certain embodiments of the present invention have described above. Itis, however, expressly noted that the present invention is not limitedto those embodiments, but rather the intention is that additions andmodifications to what was expressly described herein are also includedwithin the scope of the invention. Moreover, it is to be understood thatthe features of the various embodiments described herein were notmutually exclusive and can exist in various combinations andpermutations, even if such combinations or permutations were not madeexpress herein, without departing from the spirit and scope of theinvention. In fact, variations, modifications, and other implementationsof what was described herein will occur to those of ordinary skill inthe art without departing from the spirit and the scope of theinvention. As such, the invention is not to be defined only by thepreceding illustrative description.

What is claimed is:
 1. A system for treating a patient, the systemcomprising: a catheter; at least one retention element slidably disposedwithin the catheter; an embolic material flowable or slidable through alumen of the catheter; and an elongate body connected to the at leastone retention element; wherein the elongate body further comprises adetachable link, the detachable link being one of an electrolyticallyseverable segment, a mechanical link, and a thermally severable segment;and wherein the at least one retention element is configured to movefrom an unexpanded configuration to an expanded configuration within abody lumen and retain the embolic material substantially proximal to theat least one retention element within the body lumen.
 2. The system fortreating a patient of claim 1, wherein the detachable link is disposedbetween a portion of the elongate body connected to the at least oneretention element and another portion of the elongate body.
 3. Thesystem of claim 1, wherein the elongate body is a shape memory wire. 4.The system of claim 1, wherein the at least one retention element ismoveable between the unexpanded configuration characterized by a firstdiameter and the expanded configuration characterized by a seconddiameter larger than the first diameter.
 5. The system of claim 1,wherein the at least one retention element comprises a spiral shape. 6.The system of claim 1, wherein the at least one retention elementcomprises a plurality of cross-members.
 7. The system of claim 1,wherein the at least one retention element has a substantially planarstructure.
 8. A method of treating a patient utilizing a systemaccording to claim 1, the method comprising: inserting a distal end ofthe catheter into a blood vessel; advancing the at least one retentionelement distally from the catheter into the blood vessel; and disposingthe embolic material substantially proximally to the at least oneretention element through the catheter.
 9. A system for treating apatient, the system comprising: a catheter; an embolic material slidablydisposed within a lumen of the catheter; a first retention element and asecond retention element disposed proximally and distally about theembolic material, respectively; a pushrod comprising an elongate bodyslidably disposed within the catheter; and a link disposed on an end ofthe pushrod, the link detachably connecting the end of the pushrod tothe first retention element, the link being one of an electrolyticallyseverable segment, a mechanical link, and a thermally severable segment;wherein the second retention element is configured to move from anunexpanded configuration to an expanded configuration within a bodylumen and retain the embolic material substantially proximal to thesecond retention element within the body lumen.
 10. The system of claim9, wherein the link is a shape memory wire.
 11. The system of claim 9,wherein the embolic material absorbs water when disposed in an aqueousenvironment.
 12. The system of claim 9, wherein the embolic materialforms a gel.
 13. The system of claim 9, wherein the first retentionelement and the second retention element are connected to one another byan elongate member extending between them.
 14. The system of claim 9,wherein the embolic material is a superabsorbent polymer plug.
 15. Thesystem of claim 14, wherein the superabsorbent polymer plug includescollagen.
 16. A method of treating a patient using the system of claim9, the method comprising the steps of: inserting a distal end of thecatheter into a blood vessel of a patient; and retracting the catheterover the pushrod, thereby releasing the first retention element and thesecond retention element and the embolic material.
 17. A method oftreating a patient, comprising the steps of: forming, in a body lumen ofa patient, an occlusive structure comprising: an expandable implantconfigured to move from an unexpanded configuration to an expandedconfiguration within the body lumen; a polymer plug contacting theexpandable implant; and an elongate body connected to the expandableimplant; wherein the elongate body further comprises a detachable link,the detachable link being one of an electrolytically severable segment,a mechanical link, and a thermally severable segment; wherein thepolymer plug is formed by a liquid embolic material or a superabsorbentpolymer material; and wherein the expandable implant is configured toretain the polymer plug substantially proximal to a distalmost end ofthe expandable implant within the body lumen.
 18. The method of claim17, wherein the expandable implant includes a proximal radiallyexpandable element and a distal radially expandable element connected byat least a portion of the elongate body and the polymer plug is asuperabsorbent polymer contacting the elongate body between the proximaland distal radially expandable elements.
 19. The method of claim 17,wherein the expandable implant is a single radially expandable elementand the polymer plug is a hardened liquid embolic material contactingthe radially expandable element.
 20. The method of claim 17, wherein thedetachable link is disposed on the elongate body between a portion ofthe elongate body connected to the expandable implant and anotherportion of the elongate body.